Introduction: Cognitive impairment among older adults is often due to multiple pathologies and heterogenous risk factors. We assessed whether Alzheimer's blood-based biomarkers (BBMs) were associated with incident mild cognitive impairment (MCI)/probable dementia, and whether associations were modified by age, apolipoprotein E (APOE), and hormone therapy (HT).
Methods: Analyses included 2467 Women's Health Initiative Memory Study women (≥65 years of age) randomized between 1995 and 1998 to 3-5-years of HT or placebo. Cox regression (mean 18-year follow-up) assessed associations between the z-scored BBMs and MCI/dementia.
Results: Lower baseline amyloid beta (Aβ)42/40 ratio and higher phosphorylated tau 181 (p-tau181), glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were associated with an increased risk of MCI and dementia; GFAP was most strongly associated. The p-tau181 and NfL associations were stronger among APOE ε4 carriers; BBMs varied non-linearly by age. The associations of BBMs with the cognitive outcomes also varied inconsistently between HT groups.
Discussion: BBMs for AD and related dementias (ADRD) are associated with incident MCI/dementia in older women. Interactions between the BBMs and HT were inconsistent and require further investigation.
Keywords: Alzheimer's disease; blood‐based biomarkers; cognition; dementia; hormone therapy; mild cognitive impairment; women.
© 2026 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.